Identifying clinical and proteomic markers for early diagnosis and prognosis prediction of major psychiatric disorders.

Background: To clarify if blood proteins can predict disease progression among individuals at clinical high-risk of severe mental illness (CHR-SMI), we developed a statistical model incorporating clinical and blood protein markers to distinguish the transition group (who developed severe mental illness) (CHR-SMI-T) and from non-transition group (CHR-SMI-NT) at baseline.

Methods: Ninety individuals (74 at CHR-SMI: 16 patients) were monitored for ≤4 years and were the focus of predictive models. Three predictive models (1 [100 clinical variables], 2 [158 peptides], and 3 [100 clinical variables +158 peptides]) were evaluated using area under the receiver operating characteristic (AUROC) values. Clinical and protein feature patterns were evaluated by linear mixed-effect analysis within the model at 12 and 24 months among patients who did (CHR-SMI-T) and did not transition (CHR-SMI-NT) and the entire group.

Result: Eighteen CHR-SMI individuals with major psychiatric disorders (first episode psychosis: 2; bipolar II disorder: 13; major depressive disorder; 3) developed disorders over an average of 17.7 months. The combined model showed the highest discriminatory performance (AUROC = 0.73). Cytosolic malate dehydrogenase and transgelin-2 levels were lower in the CHR-SMI-T than the CHR-SMI-NT group. Complement component C9, inter-alpha-trypsin inhibitor heavy chain H4, von Willebrand factor, and C-reactive protein were lower in the patient than the CHR-SMI-NT group. These differences were non-significant after FDR adjustment.

Limitations: Small sample, no control for medication use.

Conclusion: This exploratory study identified clinical and proteomic markers that might predict severe mental illness early onset, which could aid in early detection and intervention. Future studies with larger samples and controlled variables are needed to validate these findings.